Proteins are now commonly used in medical fields, and represent more than half of developed drugs. Insulin, albumin, interferon or antibodies are some examples.
A protein is a polypeptide chain with a particular folding, where the folding defines certain functions of the protein. However, this folding can be easily altered, for example, where the protein is unfolded or misfolded, by heat, extremes of pH, mechanical forces, chemical denaturants, by other proteins, or just by contact with surfaces of glass or plastic, for example. Proteins stored in medical containers like syringes, cartridges, vials, ampoules, bottles or test tubes can thus be entirely inactivated within several hours.
Unfolded proteins can aggregate and form insoluble blocks, whereas misfolded proteins can have unexpected and dangerous effects on human body, both of which are undesirable.
That is why control and prevention of unwanted unfolding or misfolding of therapeutic proteins is an important and ubiquitous hurdle to be addressed during the manufacture, storage, shipping, and administration of pharmaceutical products.
Methods have been proposed to solve this problem, most of them based on biological processes. In particular, it is known to use a class of large proteins named chaperones for assisting with the folding/unfolding and the assembly/disassembly of other macromolecular structures.
In most of these known methods, the chaperones are free in the pharmaceutical solution. They can thus contribute to the refolding of unfolded proteins in the solution. However it could be interesting to benefit from the function of the chaperones without releasing the chaperones free in solution.
International Patent Publication WO00/55183 discloses immobilizing chaperones on a solid surface. This document proposes to perform this immobilization by a chemical reaction which generates covalent bonds between the chaperone and the treated surface.
Such immobilization of the chaperones prevents their releasing free in solution, while still benefiting from their refolding effect.
However, as the chemical reaction involves thiols, the chaperone can be bound to a solid surface only by a disulfide. Disulfides of chaperones (and of proteins in general) form structural constraints necessary to keep them in their native conformation. Due to the formation of covalent bonds in the chemical reaction described in International Patent Publication WO00/55183, at least one disulfide bridge is destroyed and there is a risk for the chaperone not to remain in its native conformation and to loose its activity after such chemical modification.
Moreover, if the chaperone does not contain a disulphide, it cannot be bound.
It is a general object of the invention to improve known methods such as mentioned above. In particular, it is an object of the invention to prevent release of chaperones or fragments of chaperones in pharmaceutical solutions without altering their efficiency against protein unfolding. In addition, it is an object of the present invention to provide an improved container for a pharmaceutical compound having a protein component. The improved container according to the present invention is an improvement over known containers with respect to the inner surface coating of the container and its improved effect on a pharmaceutical compound having a protein component.
It is another object of the invention to provide a method which can apply to any chaperone.